Highlights

NeuroCart®, a comprehensive neurological and psychological test battery developed at CHDR, is used to link pharmacological mechanisms to relevant functional CNS domains

Validated pharmacological challenge tests can be used to demonstrate specific CNS effects in healthy subjects

Additional applications include neuroimaging techniques such as resting-state functional magnetic resonance imaging (rs-fMRI) and positron emission tomography (PET), which are used to confirm that the relevant targets and/or networks are reached.

Summary

A powerful example of this approach is NeuroCart®, which is used to characterise the pharmacological effects of compounds on a wide range of neurophysiological and neuropsychological functions in both healthy subjects and patients. NeuroCart can also be used to measure functional diagnostic processes in psychopathology. In addition, CHDR has a highly effective recruitment strategy, allowing researchers to recruit patient cohorts with a various psychiatric conditions. Importantly, in studies involving psychiatric patients, CHDR collaborates closely with the patients’ own healthcare professionals in order to ensure continuity of care

Taking care of patients

Using the information obtained in early-phase clinical studies, researchers can design patient studies that are both safe and clinically relevant. CHDR has performed many trials in patient cohorts with a wide range of psychiatric disorders, and patient care always has the highest priority. Thus, when recruiting patients and obtaining informed consent, CHDR complies with the highest standards of medical ethics. Before, during, and after each study, the patients’ safety and well-being are ensured by informing the patient’s general practitioner and the attending psychiatrist regarding the details of the study.

Ready-for-Research

CHDR has also developed an innovative approach to recruiting patients. With Ready-for-Research, we can recruit and pre-screen patients who are interested in participating in future studies, and we can establish their baseline CNS functions using NeuroCart®. This approach ensures that when a specific study is ready to begin, CHDR already has a suitable patient cohort on hand. Using both functional and ‘wet’ biomarkers, we can also quantify systems that are relevant to the specific disease (for example, by measuring the hypothalamus-pituitary-adrenal axis and pro-inflammatory, before a clinical study is even ready, we’ve already performed an observational trial in these patients.

Practical answers to important research questions

Does our compound have the desired effect?

Our combined approach allows CHDR researchers to assess whether novel compounds have the desired effect on CNS function. For example, to study a selective new GABAA α2α3 receptor agonist developed for treating anxiety disorders, CHDR researchers used NeuroCart® and found that the compound likely has anxiolytic effects in patients.

What is the optimal dose for testing our compound in patients?

Continuing the example above, the results of our early-stage clinical studies enabled us to determine the optimal pharmacologically active dose for future trials in patients with anxiety disorders.
CHDR has also played a central role in developing a rapidly dissociating dopamine receptor D2 antagonist. Researchers used a NeuroCart® test to measure D2 receptor antagonism, thereby estimating the optimal oral dose for maximum D2 receptor occupancy.

NeuroCart®: The next generation of multifunction, standardised CNS test batteries

fMRI: A powerful tool for measuring the pharmacodynamics of new drugs in the fields of psychiatry and neurology

CHDR is a pioneer in resting-state functional magnetic resonance imaging (RS-fMRI), a powerful tool for measuring the pharmacodynamics of new drugs in the fields of psychiatry and neurology. To develop and test clinical applications for RS-fMRI, CHDR works closely with the Pharmaco-MRI Research Unit at Leiden University Medical Centre (LUMC).